Mammalian prion protein (PrP) forms conformationally different amyloid intracellular aggregates in bacteria

Microbial Cell Factories

Research

Yraima Cordeiro¹  Bruno Macedo²  Ricardo Sant’Anna³  Susanna Navarro⁴  Salvador Ventura⁴ 

[1] Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco B, Subsolo, Sala 17, 21941-902, Rio de Janeiro, RJ, Brazil;Faculdade de Farmácia, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Bloco B, Subsolo, Sala 17, 21941-902, Rio de Janeiro, RJ, Brazil;Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;CAPES Foundation, Ministry of Education of Brazil, 70040-020, Brasilia, DF, Brazil;Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;Departament de Bioquímica i Biologia Molecular, Facultat de Biociències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain;

关键词: Mammalian prions;    Protein aggregation;    Protein conformation;    Inclusion bodies;    Amyloids;    E. coli;   

DOI  :  10.1186/s12934-015-0361-y

 received in 2015-07-06, accepted in 2015-10-17,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAn increasing number of proteins are being shown to assemble into amyloid structures that lead to pathological states. Among them, mammalian prions outstand due to their ability to transmit the pathogenic conformation, becoming thus infectious. The structural conversion of the cellular prion protein (PrPC), into its misfolded pathogenic form (PrPSc) is the central event of prion-driven pathologies. The study of the structural properties of intracellular amyloid aggregates in general and of prion-like ones in particular is a challenging task. In this context, the evidence that the inclusion bodies formed by amyloid proteins in bacteria display amyloid-like structural and functional properties make them a privileged system to model intracellular amyloid aggregation.ResultsHere we provide the first demonstration that recombinant murine PrP and its C-terminal domain (90–231) attain amyloid conformations inside bacteria. Moreover, the inclusions formed by these two PrP proteins display conformational diversity, since they differ in fibril morphology, binding affinity to amyloid dyes, stability, resistance to proteinase K digestion and neurotoxicity.ConclusionsOverall, our results suggest that modelling PrP amyloid formation in microbial cell factories might open an avenue for a better understanding of the structural features modulating the pathogenic impact of this intriguing protein.

【 授权许可】

CC BY   
© Macedo et al. 2015